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Biomedical subjects

G Alth

Publications and source records attributed to G Alth.

At least 19 recordsLinked to original sources
PubMed2005

Hypericin--the facts about a controversial agent.

Hypericin is a naturally occurring substance found in the common St. John's Wort (Hypericum species) and can also be synthesized from the anthraquinone derivative emodin. As the main component of Hypericum perforatum, it has traditionally been used throughout the history of folk medicine. In the last three decades, hypericin has also become the subject of intensive biochemical research and is proving to be a multifunctional agent in drug and medicinal applications. Recent studies report antidepressive, antineoplastic, antitumor and antiviral (human immunodeficiency and hepatitis C virus) activities of hypericin; intriguing information even if confirmation of data is incomplete and mechanisms of these activities still remain largely unexplained. In other contemporary studies, screening hypericin for inhibitory effects on various pharmaceutically important enzymes such as MAO (monoaminoxidase), PKC (protein kinase C), dopamine-beta-hydroxylase, reverse transcriptase, telomerase and CYP (cytochrome P450), has yielded results supporting therapeutic potential. Research of hypericin and its effect on GABA-activated (gamma amino butyric acid) currents and NMDA (N-methyl-D-aspartat) receptors also indicate the therapeutic potential of this substance whereby new insights in stroke research (apoplexy) are expected. Also in the relatively newly established fields of medical photochemistry and photobiology, intensive research reveals hypericin to be a promising novel therapeutic and diagnostic agent in treatment and detection of cancer (photodynamic activation of free radical production). Hypericin is not new to the research community, but it is achieving a new and promising status as an effective agent in medical diagnostic and therapeutic applications. New, although controversial data, over the recent years dictate further research, re-evaluation and discussion of this substance. Our up-to-date summary of hypericin, its activities and potentials, is aimed to contribute to this process.

Animals↗
PubMed1999

5-aminolevulinic acid-mediated photodynamic therapy of intraepithelial neoplasia and human papillomavirus of the uterine cervix--a new experimental approach.

The aim of this study was to treat patients for ectocervical dysplasia [cervical intraepithelial neoplasia (CIN) grades 1 and 2] and associated human papilloma virus (HPV) infections with photodynamic therapy (PDT). In 20 patients, 5-aminolevulinic acid (5-ALA, 12% w/v) was applied topically with a cervical cap 8 h prior to illumination. A thermal light source (150 W halogen lamp) emitting a broadband red light (total energy: 100 J/cm2, fluence rate: 90 mW/cm2) was used for superficial illumination of the portio. In addition, an Nd:YAG pumped dye laser (652 nm) was used to illuminate the cervical canal (total energy: 50 J/cm2, fluence rate: 300 mW/cm2). Preliminary results of follow-ups at 1, 3, 6, and 9 months posttherapy showed a cytological improvement in the grading of the PAP smears in 19 patients and the eradication of cervical HPV in 80%. These results demonstrate that ectocervical dysplasia and associated HPV infections can be treated by PDT.

Administration, Intravaginal↗
PubMed1999

Antagonistic effects of combination photosensitization by hypericin, meso-tetrahydroxyphenylchlorin (mTHPC) and photofrin II on Staphylococcus aureus.

Photodynamic therapy involves the application of a photosensitizer activated by visible light to generate cytotoxic reactive oxygen. In addition to clinical investigations, in vitro studies concerning photodynamic potency of sensitizers as well as quantification of illumination procedures are necessary. In our investigation, the objective was to evaluate not only the effects of photosensitizer and light on Gram-positive Staphylococcus aureus, but also to investigate possible synergistic or antagonistic effects of these sensitizers. Therefore, we used hypericin, Photofrin II, porfimer sodium and meso-tetrahydroxyphenylchlorin (mTHPC) alone, as well as in combination. Log-phase cells of S. aureus exhibited a marked sensitivity to white thermal light irradiation in the presence of Photofrin II and mTHPC. However, hypericin caused a rather stimulated growth expressed in increased optical density (OD) and increase of total cell count (TCC) of the culture. Combination sensitization of S. aureus by Photofrin II and mTHPC with hypericin likewise caused a stimulation of bacterial growth. No synergistic effects were obtained by combination of Photofrin II and mTHPC; photoresponse of S. aureus was rather decreased by using combined porphyrins. In comparison, TCC and colony-forming units (CFU) were suppressed in the presence of mTHPC after an illumination procedure as well as in dark reactions. These effects were also obtained in the combination photosensitization by mTHPC and Photofrin II. In the presence the of hypericin, photodynamic effects of mTHPC and Photofrin II were inhibited. It was finally concluded that hypericin in our model is not a proper sensitizer for combination photo-sensitization due to antagonistic effects on photodynamic activity of mTHPC and Photofrin II.

Cell Culture Techniques↗
PubMed1999

Ambulant photodynamic therapy of superficial malignomas with 5-ALA in combination with folic acid and use of noncoherent light.

This study reports our first results of ambulant photodynamic treatment with 5-aminolevulinic acid (5-ALA) in combination with folic acid and subsequent illumination with a noncoherent light source. The compound was topically applied to avoid total body skin sensitivity which occurs in the case of systemic administration. If no therapeutic response could be proved, we added folic acid to 5-ALA for a further treatment attempt. Illumination was performed by broad band red thermic light to also excitate reaction products with absorption bands located near to that of the sensitizer. As a result, we observed a response in all cases, however, in some cases only after the addition of folic acid.

Administration, Topical↗
PubMed1997

Measurement of inotropic effects by a newly developed guinea pig papillary muscle bioassay.

In order to measure inotropic influences of physiologically occurring substances and drugs we used a newly developed guinea pig papillary muscle (GPPM) bioassay. GPPM were suspended in air and surface coated with buffer (Krebs-Henseleit solution). The muscles were stimulated (pulsating direct current, 1.5 V; 0.5 Hz, 20 ms duration) which led to contraction. This method enables measurements of inotropic effects up to 5 days, contrary to previous studies (1 day), in which immersions of GPPM in buffer were performed. In order to investigate the comparability of the new method we measured the effect of metabolites (citric acid cycle), lactic acid, lactate, and extracellular pH on muscle contractility. The H(+)-dependent decrease of the contractile force of the GPPM can be compensated by an increased Ca(2+)-concentration. Further, the influence of catecholamines (isoproterenol) on the contractility was investigated. As a result, isoproterenol caused arrhythmias and extrasystoles as it was observed in clinical studies. Several pharmaceutical substances were tested to show the reproducibility and repeatability of the bioassay.

Acid-Base Equilibrium↗
PubMed1996

Induratio penis plastica: effectivity of low-dose radiotherapy at different clinical stages.

This study describes the treatment of Peyronie's disease by means of low-dose radiotherapy. We treated 265 men aged 24.5-79.4 years (median = 57.7 years). No previous therapy had been carried out in 214 patients, and 41 patients had been pretreated (systemic: potassium p-aminobenzoate, vitamins a, b, e; topical: corticosteroids, teleradiotherapy). The disease was classified using criteria proposed by Alth in 1984 location, number and size of foci, hardness of fibromatous foci and axis deviation, potentia coeundi and pain were evaluated). Radiotherapy was performed by local application of a special iridium-192 moulage developed at our institute. In 66.4% of the monitored patient group (n = 155) therapy was successful. We obtained complete regression of the fibromatous foci in 9% (n = 14), partial remission > 50% in 29.7% (n = 46) and partial remission < 50% in 27.7% (n = 43) of the patients. We found a significant correlation between hardness, size of the treated foci and therapeutic success. Eighty-three patients suffered from pain during penile erection before therapy, and in 61.4% (n = 51) of these patients the pain disappeared after treatment. Moreover, the patients confirmed that both loss of pain and regression of deviation related to foci regressions were correlated with improvement in erectile function. No serious side effects were observed in any of our patients.

Adult↗
PubMed1996

Natural products derived from plants as potential drugs for the photodynamic destruction of tumor cells.

Chlorophyll and some of its synthetically produced derivatives are important sensitizers in photodynamic cancer therapy. Other natural products from plants with light dependent activity include quinones like hypericin and fagopyrin. These compounds have extended pi-electron systems which upon photoexcitation with visible light are responsible for singlet oxygen production. Other plant constituents which show UV light induced photosensitizing activity are furanocumarins like psoralen and angelicin, aflatoxins and alkaloids, as well as thiophene derivatives, terthienyl and several polyacetylenes. The photodynamic properties of a chelidonium alkaloid derivative and data for its potential clinical applicability are given.

Antineoplastic Agents↗
PubMed1996

Wavelength-dependent photoresponse of biological and aqueous model systems using the photodynamic plant pigment hypericin.

Photodynamic eradication of tumour cells in vivo depends on the presence of a photosensitizer, light delivery to the cells, and an oxygen supply. Hypericin, a polycyclic quinone with absorption maxima in the ultraviolet and visible ranges, was prepared for clinical use as a photosensitizer. Due to antitumoral and antineoplastic activities as well as the generation of singlet oxygen after photoexcitation, hypericin was applied in clinical oncology and photodynamic therapy. Hypericin was administered subcutaneously (20 micrograms hypericin in 200 microliters Nacl/pyridine solution) into the ante brachium (forearm) of two volunteers. After the diffusion and equilibration of 120 min phototesting was carried out using outdoor light exposure, halogen lamp, laser 514 nm (argon), laser 632 nm (argon dye) and laser 670 nm (diode laser), from 60 to 120 J cm-2. Positive phototests to outdoor light exposure, halogen lamp and laser 514 nm were characterized by rubescence, oozing, vesiculation and darting pain. Phototests with laser 632 nm and 670 nm showed no effects after irradiation. When hypericin was administered topically on skin, erythema and flaring could not be induced by any irradiation. These results suggest that hypericin is a potent photosensitizer only within the UV and green light ranges. This characteristic photoresponse could also be obtained in guinea pig papillary muscle (GPPM) bioassay, which may be established as a model for photosensitizer testing. Irradiation of hypericin-incubated GPPM with 514 nm (20 J cm-2) led to a decrease of the contractile force of about 31%. However, excitation with 632 nm and 670 nm did not cause inotropic effects on GPPM. In addition, hypericin and Photosan 3 were shown to be capable of sensitizing the photo-oxidation of sodium linoleate. This assay should be established for testing interactions between photosensitizers and light sources in vitro.

Animals↗
PubMed1996

Hypericin in phototherapy.

We describe the first local use of hypericin as photosensitizer for photodynamic therapy in a patient with recurrent malignant mesothelioma. Hypericin is a polycyclic quinone, which has been shown to possess in vivo and in vitro antiretroviral and photosensitizing activity; moreover, it is used in depressive disorders. The semiquinone radical, singlet oxygen, and superoxide anion radical are reported to be the toxic agents in hypericin phototherapy. Our first experience with locally applied hypericin in a superficial tumor-plate was performed 8 weeks after the systemic administration of hematoporphyrin derivatives. For tumor light illumination we used an argon pumped dye laser tuned to 632 nm. Owing to satisfactory results, we repeated the same therapy 4 weeks later- and no therapeutic effect was noted. Following this, we proved the interstitial application of HPD and the combination of interstitial HDP and superficially applied hypericin. The subsequent light illumination 6 hours later had no efficacy in the HDP-photosensitized area but there was tumor destruction in the field with both administered photosensitizers. Our first experience suggests a potentiation of two photosensitizers: hematoporphyrin derivatives and hypericin.

Aged↗
PubMed1996

Determination of Photosan III in human plasma.

In order to develop an accurate and quick method for the determination of Photosan III in human plasma, we used statistically planned experiments with an aim to identify the factors that can influence the analysis. Through a series of 20 experiments based on acid extraction of the porphyrin from the plasma and subsequent fluorescence analysis a calibration was obtained between 0 and 3.3 x 10(-5) M. The deviation of the parameters around the regression line is 3.02%, the coefficient of variation 3.55%.

Adult↗
PubMed1996

Photodynamic therapy in gynaecologic cancer.

We started photodynamic therapy in gynaecologic tumors in 1988. Seven patients with endometrial carcinomas stage FIGO 1a (restricted to the endometrium) were treated primarily and also 4 patients with recurrences of vaginal and vault cervix carcinoma, carcinoma of the corpus uteri and the vulva. Residual tumors after conventional therapy of cervix and vulvar carcinoma were treated in 2 patients. Tumor illumination was performed by an Argon dye laser 24-72 h following the intravenous administration of haematoporphyrin derivatives (HPD) (Photosan III, 2 mg kg-1 body weight). The intracavitary tumor irradiation by means of a glass fibre was controlled by ultrasound. Superficial and small lesions of vaginal and vulvar carcinomas were subjected to superficial light irradiation; whereas tumors exceeding 1 cm in depth were treated interstitially. Tumor response was estimated 1 month after therapy. Complete remission was achieved in 8 patients, partial remission in 2, and no remission in 3 cases. Subsequent radiotherapy was performed in 3 patients with bleeding endometrial cancer with consecutive complete response.

Adenocarcinoma↗
PubMed1996

Experiences of photodynamic therapy in dermatology.

From March 1988 to May 1994, 15 patients underwent the treatment protocol of superficial photodynamic therapy (PDT) in dermatological localized malignancies. Two tumours (one M. Queyrat of the penis, one basalioma) were treated primarily; the other 13 patients experienced relapses of underlying disease after treatment by surgery, radiotherapy or chemotherapy. Most of the patients (10/15) received doses of 2 mg Photosan III kg-1 body weight (BW), four received a lower dose of 1-1.5 mg kg-1 BW and one patient received 3 mg kg-1 BW. Only one remarkable side-effect (tachyarrhythmia) during Photosan III infusion occurred. All patients were treated by an argon dye laser system. The light dose was 200 J cm-2 (11 patients) and 150 J cm-2 (four patients). Complete response occurred in six lesions, including one M. Queyrat and five basaliomas. Two patients had significant partial response with distinct regression of tumour (one pretreated basalioma of the upper lip and one superficially spreading mesothelioma of the scrotum). Five patients (all basaliomas) demonstrated only local response and two patients gave no response (one basalioma, one melanoma metastasis). The results obtained from this small sample suggest the necessity of an optical dosimetric system. At present, PDT should be restricted for selected or pretreated cases.

Basal Cell Carcinoma↗
PubMed1996

Evaluation of Cyfra 21-1 as a marker for lung cancer.

The sensitivity and specificity of Cyfra 21-1 as marker for lung cancer was evaluated in comparison with carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and neuron-specific enolase (NSE). Patients with histologically verified lung cancer and different groups without lung cancer were investigated. Sensitivity of Cyfra 21-1 (cut-off level 2.9 micrograms/l) was 40% for non-small cell lung cancer (NSCLC), 60% for rare histological types and 21% for small cell lung cancer (SCLC). In NSCLC sensitivity of Cyfra 21-1 was 35% for squamous cell carcinoma and 41% for adenomous carcinoma. The highest sensitivity for CEA was 45% in NSCLC, with 57% in the subtype of adenomous cell carcinoma; for SCC 30% was achieved in squamous cell carcinoma and for NSE 66% sensitivity was reached in SCLC. In our patients Cyfra 21-1 and CEA appeared equally useful for evaluating patients with NSCLC.

Adult↗
PubMed1994

Photodynamic therapy--an alternative pathway in the treatment of recurrent breast cancer.

PURPOSE: Validity of photodynamic therapy for treatment of recurrent breast cancer. METHODS AND MATERIALS: Patients were intravenously administered with a metal-free haematoporphyrine derivative for tumor sensibilization. For irradiation both monochromatic and white light was used. Monochromatic light at a wavelength of 632 nm was supplied by an Argon-Dye laser, whereas a halogen lamp provided white light. Narrowband red light came into use in case of one patient. Therapy included recurrent diseases of breast carcinoma, especially disseminary skin metastases, local recurrences, and lymphangiosis. Classical pretreatment was ineffective for the therapeuted patient group. RESULTS: The healing potency of photodynamic therapy for our patient group is enumerated in detail. No differences in the therapeutic effect were seen using either Argon Dye laser or noncoherent light sources. CONCLUSION: Photodynamic therapy appears to be a valuable treatment to classical therapeutic intervention providing a selective destruction of tumor cells without further affecting life quality.

Adult↗
PubMed1993

A quantitative determination of singlet oxygen with horseradish peroxidase.

A singlet oxygen determination method based on the formation of dimethyl-(2,5)-2-methoxy-5-hydroperoxydihydrofuran (DMFO2) followed by acid hydrolysis with 0.1 N H2SO4 is described. Hydrogen peroxide is formed thereby as a product of hydrolysis which is then determined by the horseradish peroxidase-catalyzed formation of the homovanillic acid dimer. Since DMFO2 is a crystalline compound with sufficient stability it can be used as a primary standard for the determination. The peroxidase-catalyzed hydrogen peroxide determination allows detection of singlet oxygen concentrations as low as 10(-7) M.

Free Radicals↗